Articular cartilage serves as the load-bearing material of joints, with excellent friction, lubrication and wear characteristics. It is a white, dense, connective tissue, from 1 to 7 mm thick, that covers the bony articulating ends inside the joint. Due to its avascular nature, cartilage exhibits a very limited capacity to regenerate and to repair. Moreover, it has been stated that the natural response of articular cartilage to injury is variable and, at best, unsatisfactory. The clinical need for improved treatment options for the numerous patients with cartilage injuries has motivated tissue engineering studies aimed at the in vitro generation of cartilage replacement tissues (or implants) using chondrocyte seeded scaffolds. Although much of the tissue engineered cartilage in existence has been successful in mimicking the morphological and biochemical appearance of hyaline cartilage, they are generally mechanically inferior to the natural tissue. Recent developments in our understanding of cartilage biomechanics suggest that interstitial fluid pressurization and to a lesser degree tissue matrix deformation are the two predominant mechanical phenomena which exist in cartilage during joint loading, with fluid pressurization never completely subsiding under physiologic conditions. This fluid pressurization is the source of the tissue's unique load-bearing and lubrication properties. Significantly, this pressurization and deformation are coupled, occurring simultaneously and intermittently. The governing hypothesis for this proposal states that the physiologic combination of intermittent pressure and deformational loading of chondrocyte seeded 3D scaffolds is required for the optimal generation of a tissue with functional mechanical properties and biochemical composition similar to articular cartilage. No previous studies to our knowledge have combined the application of intermittent physiologic strain and hydrostatic pressure levels, the normal environment of the chondrocyte in vivo, to the study of chondrocyte biosynthetic activities nor to the development of a functional tissue matrix in a 3D scaffold culture. We will use a custom bioreactor capable of simultaneously subjecting cell-seeded scaffold disks to applied hydrostatic pressure and deformations at physiologic levels. The most current techniques for measuring cartilage mechanical properties will be used to assess the development of a functional tissue. Together, with cell metabolism studies and tissue compositional analyses, new information regarding the effect of simultaneously applied hydrostatic pressure and deformational loading on chondrocyte biosynthetic activity and its potential for promoting cartilage growth in vitro will be provided. The ability to restore the tissues ability to pressurize, the source of its load-bearing and lubrication properties, will ameliorate the pain and suffering arising from OA, a debilitating disease which results in the erosion of diarthrodial joint cartilage. Currently, OA affects 5 percent of the general population and 70 percent of the population over age 65 and costs nearly 8 billion dollars annually in health care.
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